Proteomics Analysis of Monocyte-Derived Hepatocyte-Like Cells Identifies Integrin Beta 3 as a Specific Biomarker for Drug-Induced Liver Injury by Diclofenac

Frontiers in Pharmacology
Diana DragoiAlexander L Gerbes

Abstract

Idiosyncratic drug-induced liver injury (iDILI) is a major cause of acute liver failure resulting in liver transplantation or death. Prediction and diagnosis of iDILI remain a great challenge, as current models provide unsatisfying results in terms of sensitivity, specificity, and prognostic value. The absence of appropriate tools for iDILI detection also impairs the development of reliable biomarkers. Here, we report on a new method for identification of drug-specific biomarkers. We combined the advantages of monocyte-derived hepatocyte-like (MH) cells, able to mimic individual characteristics, with those of a novel mass spectrometry-based proteomics technology to assess potential biomarkers for Diclofenac-induced DILI. We found over 2,700 proteins differentially regulated in MH cells derived from individual patients. Herefrom, we identified integrin beta 3 (ITGB3) to be specifically upregulated in Diclofenac-treated MH cells from Diclofenac-DILI patients compared to control groups. Finally, we validated ITGB3 by flow cytometry analysis of whole blood and histological staining of liver biopsies derived from patients diagnosed with Diclofenac-DILI. In summary, our results show that biomarker candidates can be identified by prot...Continue Reading

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Citations

Mar 14, 2019·Current Opinion in Gastroenterology·Hans L TillmannDon C Rockey
Feb 23, 2020·Frontiers in Pharmacology·Siyu FuTaoyou Zhou
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Nov 4, 2021·Expert Opinion on Drug Metabolism & Toxicology·Edmond AtallahGuruprasad P Aithal

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Datasets Mentioned

BETA
PXD008918

Methods Mentioned

BETA
Assay
biopsy
PCA
flow cytometry
biopsies
FACS

Clinical Trials Mentioned

NCT02353455

Software Mentioned

Heat Map
DicloDILI
RUCAM
MaxQuant
Andromeda
SPSS Statistics
SPSS
SprayQC
Perseus
DILI

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